Resistant starch type-2 enriched cookies modulate uremic toxins and inflammation in hemodialysis patients: a randomized, double-blind, crossover and placebo-controlled trial

Esgalhado, Marta; Kemp, Julie Ann; Paiva, Bruna R.; Brito, Jessyca Sousa de; Cardozo, Ludmila F M F; Azevedo, Rui; Cunha, Diana Barbosa; Nakao, Lia S.; Mafra, Denise

doi:10.1039/c9fo02939g

Cited by 27 publications

(36 citation statements)

References 54 publications

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“…[ 24 ] Also, RS2 was able to increase the messenger ribonucleic acid (mRNA) nuclear erythroid 2‐related factor (Nrf2) and NAD(P)H quinone dehydrogenase 1 (NQO1) protein expression, which are related to anti‐inflammatory and anti‐oxidative stress mechanisms. [ 25 ]…”

Section: Introductionmentioning

confidence: 99%

The Impact of Enriched Resistant Starch Type‐2 Cookies on the Gut Microbiome in Hemodialysis Patients: A Randomized Controlled Trial

Kemp

Paiva

Santos

et al. 2021

Molecular Nutrition Food Res

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Introduction Resistant starch type‐2 (RS2) can mitigate inflammation and oxidative stress in hemodialysis (HD) patients. However, there is still a lack of knowledge on the impact of the RS2 on the gut microbiota community in these patients. Thus, this study aims to evaluate the effects of enriched RS2 cookies on the gut microbiome in HD patients. Methods and Results This comprises a randomized, double‐blind, placebo‐controlled trial of age‐, sex‐, and BMI‐matched patients and controls. The RS2 group receives enriched RS2 cookies (16 g d‐1 of Hi‐Maize 260, Ingredion) for 4 weeks, while the placebo group received cookies made with manioc flour. Fecal microbiota composition is evaluated by the 16S ribosomal RNA gene. Analysis of the microbiota reveals that Pielou's evenness is significantly decreased after RS2 supplementation. Notably, it is observed that RS2 intervention upregulates significantly 8 Amplicon Sequencing Variants (ASV's), including Roseburia and Ruminococcus gauvreauii, which are short‐chain fatty acids (SCFA) producers. Furthermore, it is associated with the downregulation of 11 ASVs, such as the pro‐inflammatory Dialister. Conclusions RS2 intervention for 4 weeks in HD patients effectively alters SCFA producers in the gut microbiota, suggesting that it could be a good nutritional strategy for patients with chronic kidney disease (CKD) on HD.

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Section: Introductionmentioning

confidence: 99%

The Impact of Enriched Resistant Starch Type‐2 Cookies on the Gut Microbiome in Hemodialysis Patients: A Randomized Controlled Trial

Kemp

Paiva

Santos

et al. 2021

Molecular Nutrition Food Res

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“…In a study with CKD rats, RS attenuated the inflammation [67]; however, in clinical studies, the results are still discordant. While, in one study, a reduction in some inflammatory markers was observed (TNF-α and IL-6) [68], in another, with the same dose of RS, no difference was found in the levels of hsCRP and IL-6 of HD patients [36]. Some limitations and strengths of the present study should be acknowledged.…”

Section: Discussionmentioning

confidence: 60%

“…Regarding the other two gut-derived uremic toxins evaluated (pCS and IAA), no impact of UBF was observed. Similarly, no difference in the serum total pCS was observed in other RS intervention studies with HD patients [34,36]. In healthy individuals, the production of IS and pCS does not seem to be correlated [28], suggesting that the regulation of their production occurs by different factors.…”

Section: Discussionmentioning

confidence: 77%

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Effect of Unripe Banana Flour on Gut-Derived Uremic Toxins in Individuals Undergoing Peritoneal Dialysis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

et al. 2021

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In chronic kidney disease (CKD), the accumulation of gut-derived metabolites, such as indoxyl sulfate (IS), p-cresyl sulfate (pCS), and indole 3-acetic acid (IAA), has been associated with the burden of the disease. In this context, prebiotics emerge as a strategy to mitigate the accumulation of such compounds, by modulating the gut microbiota and production of their metabolites. The aim of this study was to evaluate the effect of unripe banana flour (UBF—48% resistant starch, a prebiotic) on serum concentrations of IS, pCS, and IAA in individuals undergoing peritoneal dialysis (PD). A randomized, double-blind, placebo-controlled, crossover trial was conducted. Forty-three individuals on PD were randomized to sequential treatment with UBF (21 g/day) and placebo (waxy corn starch—12 g/day) for 4 weeks, or vice versa (4-week washout). The primary outcomes were total and free serum levels of IS, pCS, and IAA. Secondary outcomes were 24 h urine excretion and dialysis removal of IS, pCS, and IAA, serum inflammatory markers [high-sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), interleukin-10 (IL-10), and tumor necrosis factor-α (TNF-α)], serum lipopolysaccharide LPS, and dietary intake. Of the 43 individuals randomized, 26 completed the follow-up (age = 55 ± 12 years; 53.8% men). UBF did not promote changes in serum levels of IS (p = 0.70), pCS (p = 0.70), and IAA (p = 0.74). Total serum IS reduction was observed in a subgroup of participants (n = 11; placebo: median 79.5 μmol/L (31–142) versus UBF: 62.5 μmol/L (31–133), p = 0.009) who had a daily UBF intake closer to that proposed in the study. No changes were observed in other secondary outcomes. UBF did not promote changes in serum levels of IS or pCS and IAA; a decrease in IS was only found in the subgroup of participants who were able to take 21g/day of the UBF.

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“…NRF2 null mice have exaggerated and accelerated kidney injury, and conversely, NRF2 activating supplements have been shown to improve kidney function (as reviewed in [38]). Studies in patients with end stage renal dis-ease have shown increased NRF2 expression in response to dietary interventions, including administration of starch-enriched cookies [39], and brazil nut supplementation [40], though these studies did not correlate these NRF2 expression changes with clinical measures. A third pilot study involving curcumin showed no change in NRF2 mRNA expression [41].…”

Section: End-stage Renal Diseasementioning

confidence: 96%

Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease

2020

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Nuclear factor erythroid 2-related factor 2 (NRF2), a transcription factor which plays a critical role in maintenance of cellular redox, has been identified as a therapeutic target in a number of human diseases. Several reports have demonstrated beneficial effects of NRF2 manipulation in animal models of disease, and one NRF2-activating drug, dimethyl fumarate, is already approved for the treatment of multiple sclerosis. However, drug discovery is slowed due to a dearth of biomarkers which can inform target engagement and magnitude and duration of action. Peripheral blood mononuclear cells (PBMCs) are an accessible, minimally-invasive source of biomarkers which can be readily assayed and objectively monitored as a surrogate endpoint of NRF2 activation in clinical trials. We undertook a review of the literature on PBMC NRF2 measurements in human studies to explore its role as a suitable biomarker in various contexts of health and disease. It is clear that NRF2 and its target genes can be readily assayed from PBMCs in multiple disease contexts and may track with disease progression. Further work needs to be undertaken to evaluate its stability but should be considered as an exploratory marker in clinical trials targeting NRF2 activation.

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Resistant starch type-2 enriched cookies modulate uremic toxins and inflammation in hemodialysis patients: a randomized, double-blind, crossover and placebo-controlled trial

Abstract: The study evaluated the effect of resistant starch enriched cookies supplementation on the mRNA expression of nuclear transcription factors involved with inflammation and uremic toxins levels produced by the gut microbiota in hemodialysis patients.

Cited by 27 publications

References 54 publications

The Impact of Enriched Resistant Starch Type‐2 Cookies on the Gut Microbiome in Hemodialysis Patients: A Randomized Controlled Trial

The Impact of Enriched Resistant Starch Type‐2 Cookies on the Gut Microbiome in Hemodialysis Patients: A Randomized Controlled Trial

Effect of Unripe Banana Flour on Gut-Derived Uremic Toxins in Individuals Undergoing Peritoneal Dialysis: A Randomized, Double-Blind, Placebo-Controlled, Crossover Trial

Peripheral Blood NRF2 Expression as a Biomarker in Human Health and Disease

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